Relative abundance of ASA in the cell lysate (G)and the media (H)detected by LC-MS. We independently treated primary fibroblasts from two different individuals in duplicates (four biological replicates) with 85 ng RNA of the mRNA-1273 lipid nanoparticle ABE8e plus the variant-targeting sgRNA (LNP-ABE8e), or with vehicle (not treated), or with mRNA-1273 lipid nanoparticle ABE8e containing the sgRNA site_16 targeting an unrelated locus (non-targeting sgRNA). As a control, we used fibroblasts coming from three healthy donors of different genders and ages (healthy donors, three biological replicates). Two weeks after the treatment, we analyzed the metabolite content of each condition, processing five technical replicates of each sample in the LC-MS. As expected, in some of the control and edited samples the ASA levels were below the detection limit of the mass spectrometer. We did not consider these values for the graph bar or the statistical analysis, but we illustrated these cases with a shape containing a black center. Relative abundance is the absolute abundance value normalized to the sum of all metabolites. Data are represented as the mean SEM. Statistical significance based on Tukey test; p > 0.05 (ns, not significant), p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), p < 0.0001 (****).
